Cellular Engineering and Isotope Diagnostics Laboratory, Department of Physiology, Jagiellonian University Medical College, Poland.
Cellular Engineering and Isotope Diagnostics Laboratory, Department of Physiology, Jagiellonian University Medical College, Poland.
Biochem Pharmacol. 2022 Jul;201:115058. doi: 10.1016/j.bcp.2022.115058. Epub 2022 Apr 28.
Gastrointestinal (GI) tract cancers pose a significant pharmacological challenge for researchers in terms of the discovery of molecular agents and the development of targeted therapies. Although many ongoing clinical trials have brought new perspectives, there is still a lack of successful long-term treatment. Several novel pharmacological and molecular agents are being studied in the prevention and treatment of GI cancers. On the other hand, pharmacological tools designed to release an endogenous gaseous mediator, carbon monoxide (CO), were shown to prevent the gastric mucosa against various types of injuries and exert therapeutic properties in the treatment of GI pathologies. In this review, we summarized the current evidence on the role of CO and heme oxygenase 1 (HO-1) as a CO producing enzyme in the pathophysiology of GI tumors. We focused on a beneficial role of HO-1 and CO in biological systems and common pathological conditions. We further discussed the complex and ambiguous function of the HO-1/CO pathway in cancer cells with a special emphasis on molecular and cellular pro-cancerous and anti-cancer mechanisms. We also focused on the role that HO-1/CO plays in GI cancers, especially within upper parts such as esophagus or stomach.
胃肠道（GI）癌症在发现分子药物和开发靶向治疗方面对研究人员构成了重大的药理学挑战。尽管许多正在进行的临床试验带来了新的视角，但仍缺乏成功的长期治疗方法。一些新型的药理学和分子药物正在研究用于预防和治疗胃肠道癌症。另一方面，旨在释放内源性气态介质一氧化碳（CO）的药理学工具已被证明可预防胃黏膜免受各种类型的损伤，并在胃肠道疾病的治疗中发挥治疗特性。在这篇综述中，我们总结了 CO 和血红素加氧酶 1（HO-1）作为 CO 产生酶在胃肠道肿瘤病理生理学中的作用的现有证据。我们专注于 HO-1 和 CO 在生物系统和常见病理条件下的有益作用。我们进一步讨论了 HO-1/CO 途径在癌细胞中的复杂和模糊功能，特别强调了促癌和抗癌的分子和细胞机制。我们还关注了 HO-1/CO 在胃肠道癌症中的作用，特别是在上部胃肠道，如食管或胃。
